"Activity was observed in both squamous and nonsquamous non-small cell lung cancer patients treated with atezolizumab," said Vansteenkiste. "Atezolizumab was well tolerated, with a safety profile consistent with previous studies and distinct from chemotherapy."

Reinforcing the potential value of patient selection by PD-L1 values, a single-arm phase II trial of atezolizumab in NSCLC showed higher response rates in patients with the highest PD-L1 levels.

Randomized Trial

Vansteenkiste reported findings from a randomized phase II trial involving unselected patients with metastatic or locally advanced NSCLC that had progressed on prior platinum-based chemotherapy. The patients were randomized to atezolizumab or docetaxel, continuous therapy until disease progression. Stratification factors included PD-L1 expression on immune cells.

The primary objective was estimated overall survival by intention-to-treat (ITT) analysis and by PD-L1 expressions subgroups. Secondary objectives included estimated progression-free survival (PFS), objective response rate, and duration of response by ITT and by PD-L1 expression.

The primary analysis included 287 patients who had a median age of 62. A third of the patients received atezolizumab or docetaxel as third-line therapy. The results demonstrated a 27% reduction in the survival hazard with atezolizumab (HR 0.73, 95% CI 0.53-0.99, P=0.040).

In contrast, atezolizumab performed no better than docetaxel among patients with unmeasurable PD-L1 expression (9.7 months in each group, HR 1.04).

Analysis of the results by tumor histology showed a hazard ratio of 0.69 in favor of atezolizumab among patients with nonsquamous NSCLC and 0.80 for the subgroup of patients with squamous-cell tumors.

PD-L1 status by T-cell or immune-cell assessment proved to be an independent predictor of survival improvement with atezolizumab, said Vansteenkiste. Various comparisons of any PD-L1 expression versus none yielded hazard ratios of 0.37 to 0.63.

Atezolizumab did not improve median PFS in the ITT analysis (2.7 vs 3.0 months). However, stratification by PD-L1 status showed a pattern of benefit for atezolizumab similar to that observed in the analysis of overall survival, ranging from a nonsignificant hazard ratio of 0.85 for all patients with any PD-L1 expression to HR 0.60 for patients with the highest levels of PD-L1 expression (median PFS 7.8 vs 3.9 months).

The ITT analysis showed identical objective response rates of 15% in the two treatment groups. Among patients with the highest levels of PD-L1, expression had a 38% response rate with atezolizumab versus 13% with docetaxel.

Patients remained on treatment about 6 weeks longer with atezolizumab (median treatment duration 3.7 vs 2.1 months). Despite the greater exposure, atezolizumab-treated patients had about one fourth as many treatment-related grade 3/4 adverse events (11% vs 39%), and about a third as many withdrawals because of adverse events (8% vs 22%).

Investigators in a single-arm phase II trial of atezolizumab in NSCLC specifically evaluated the impact of PD-L1 expression on response to therapy, enrolling 667 patients with untreated or previously treated NSCLC, pre-selected by immunohistochemistry-determined +2 or +3 PD-L1 expression on T-cells or immune cells. The trial had a primary endpoint of objective response rate by independent review, said Benjamin Besse, MD, of Institut Gustave Roussy in Villejuif, France.

The data were stratified according to the line of therapy that atezolizumab represented. Patients with previously untreated NSCLC had an objective response rate of 19% as compared with 17% of patients who received atezolizumab as second- or third-line therapy. Limiting the analysis to patients with +3 PD-L1 expression, Besse and colleagues found that atezolizumab led to an overall response rate of 26% in first-line, 24% in second-line, and 27% in third-line.

A preliminary survival analysis showed that 82% of patients receiving first-line atezolizumab were alive at 6 months, as were 76% of second-line and 71% of third-line patients. Median overall survival was 14 months for first-line patients but not yet estimable for second- and third-line patients. Median PFS was 5.5 months with first-line atezolizumab and 2.8 months with second- and third-line therapy. The 6-month PFS was 46%, 29%, and 31% for first-, second-, and third-line therapy.

The safety profile was similar to that in the trial reported by Vansteenkiste, as 11% of patients had treatment-related grade 3/4 adverse events. The most commonly reported treatment-related grade 3/4 adverse events were fatigue, nausea, and asthenia.

"[The trial] demonstrated clinically meaningful efficacy with atezolizumab monotherapy in PD-L1-selected patients with advanced non-small cell lung cancer," Besse said in conclusion. "Higher PD-L1 expression correlates with higher response and may allow identification of patients who are likely to benefit from atezolizumab therapy."

Both studies were supported by Roche.

Vansteenkiste, Besse, and several co-investigators disclosed relevant relationships with Roche.

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